The proposed research is designed to test the hypothesis that a wide spectrum of cardiac disease and malfunction is caused by myocardial ischemia in the presence of patent coronary arteries. These conditions include low output syndrome after open heart surgery, high output cardiac failure (i.e. after pulmonary systemic shunts), papillary muscle dysfunction and sudden death after exercise. We will present a concept, support by physiologic data, which relates the metabolic demands of the myocardium to the factors determining coronary oxygen supply. Using a multi-disciplinary approach (surgeons, physiologists, biochemists, mathematician), conditions associated with clinical myocardial failure will be simulated experimentally. Regional myocardial blood supply will be measured with the radiomicrosphere method and its adequacy determined by tissue histochemical (Fuchsin) and biochemical (lactate, glycogen, creatine phosphate) analyses. The effects of myocardial preservation techniques, currently used during open heart surgery, on the distribution and adequacy of regional myocardial flow will be tested. We will attempt to show through clinical and experimental studies, that routine pressure measurements (arterial, left atrial) can be used readily to estimate the adequacy of subendocardial blood supply.